The present invention relates to methods of synthesizing certain thiazolium compounds.
In U.S. Pat. Nos. 5,656,261; 5,853,703; and 6,007,865 compounds were disclosed that are promising agents that can be used in compositions and methods useful in treating a number of indications. One mechanism of action contributing to these treatments is believed to be inhibition and reversal of nonenzymatic cross-linking (protein aging). These compounds can be used in therapeutic applications where proteins in the body deteriorate with age and as a consequence of diabetes.
Efficient syntheses for these compounds are desirable. Described herein is a surprisingly effective synthesis of a certain class of these compounds.
In one embodiment, the invention provides a method of synthesizing a compound of formula I, 
comprising: reacting a compound of formula II 
wherein R1 and R2 are independently hydrogen, hydroxy(C1-C2)alkyl, or (C1-C2)alkyl with, a compound of the formula III 
wherein R3, R4, and R5 are each independently of each other hydrogen, (C1-C3)alkyl, (C1-C3)alkoxy, or halogen; and X is a leaving group. The reaction is preferably conducted in a solvent having a dielectric constant at 20xc2x0 C. of at least 30 but no more than 40
In another embodiment, the invention provides a method of synthesizing a 4,5-dimethyl-3-(2-oxo-2-phenylethyl)-thiazolium salt comprising: reacting 4,5-dimethylthiazole with (IV), wherein X is a leaving group. 